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Clinical effect of sulbactam/ampicillin on community-acquired
pneumonia with positive Streptococcus pneumoniae urinary antigen test
Niro OKIMOTO, Koichi UCHIDA, Tadashi KATOH, Hisataka TANAKA Toshikiyo HAYASHI, Takeyuki KURIHARA, Naoyuki MIYASHITA Department of General Internal Medicine 1, Kawasaki Hospital, Kawasaki Medical School, 2-1-80, Nakasange, Kitaku, Okayama, 700-8505, Japan ABSTRACT We investigated the efficacy of intravenous penicillin (sulbactam/ampicillin:
SBT/ABPC) in adult patients with positive Streptococcus pneumoniae urinary antigen test
requiring hospitalization. We administered 3g of SBT/ABPC intravenously in the morning and
evening for 7-14 days to 32 adult community-acquired pneumonia patients with positive Binax
NOW® S. pneumoniae urinary antigen. Clinical efficacy, bacteriological efficacy, and side
effects of these patients were prospectively examined. We observed clinical efficacy in a total
of 28 of 32 patients (87.5%); 24 of 26 moderate patients (92.3%), and four of six severe patients
(66.7%). Side effects were drug eruption, increased GOT, increased AMY, and decreased
WBC, observed in one patient each; however, all were mild. SBT/ABPC is extremely useful in
patients with positive S. pneumoniae urinary antigen test requiring hospitalization

Key words: Stereptococcus pneumoniae urinary antigen test, sulbactam/ampicillin
INTRODUCTION
SUBJECTS AND METHODS
 The JRS guidelines for the management of community-acquired pneumonia in adults  Subjects were 32 patients with adult community- recommend intravenous penicillin drip if acquired pneumonia and positive S. pneumoniae Streptococcus pneumoniae urinary antigen test urinary antigen test who underwent treatment at shows positive. Therefore, we examined the clinical Kawasaki Hospital, Kawasaki Medical School from efficacy of intravenous penicillin (sulbactam/ ampicillin: SBT/ABPC) in patients with adult community-acquired pneumonia and positive  Adult community-acquired pneumonia patients S. pneumoniae urinary antigen test requiring with positive urinary antigen for S.pneumoniae (Binax NOW® S. pneumoniae) were administered Department of General Internal Medicine 1, Kawasaki Hospital, Kawasaki Medical School, 2-1-80, Nakasange, Kitaku, Okayama, 700-8505, Japan 3g of SBT/ABPC intravenously in the morning and evening for 7-14 days. Then clinical efficacy, bacteriological efficacy, and side effects of these patients were prospectively examined. This study was approved by the clinical trial review committee   Chronic obstructive pulmonary disease  Subjects were 20 males and 12 females aged 40  Severity by A-DROP system was moderate in 26  COPD (chronic obstructive pulmonary disease) was observed in four subjects, bronchial asthma in three, bronchiectasis in three, cerebrovascular                       (1)PISP                       (2)PRSP diseases in five, hypertension in five, diabetes mellitus in three, and hypothyroidism in one.  Clinical efficacy was observed in a total of 28 of 32 (87.5%) patients; 24 of 26 (92.3%) moderate patients, and in four of six (66.7%) severe patients. Efficacy was observed in three patients (PISP two, PRSP one) with penicillin-resistant S. pneumoniae. With regard to sensitivity of penicillin-G , MIC ≦2 μg , MIC =4μg , and MIC ≧8μg were judged Bacteriological efficacy (Table 4) PSSP 19 strains, PISP two strains, and PRSP one DISCUSSION
strain were isolated, and all were eradicated.  S. pneumoniae is the most frequently observed microorganism in adult community-acquired  Clinical adverse reaction was drug eruption in pneumonia, accounting for 25-39% of patients with one patient (3.1%). Abnormal laboratory findings pneumonia requiring hospitalization. Pneumonia were increased GOT, increased AMY, and decreased caused by S. pneumoniae is a potentially-severe WBC in one patient each; however, all were mild, and there were no patients whose treatment was  Gram staining and culture are useful in diagnosis. discontinued, or who received treatment for adverse Recently, S. pneumoniae urinary antigen test has been widely used in the clinical setting for rapid diagnosis. The JRS guidelines for the management of community-acquired pneumonia in adults Okimoto N, et al. : sulbactam/ampicillin on Streptococcus pneumoniae pneumonia recommend S. pneumoniae urinary antigen test to 32 (87.5%) patients; 24 of 26 (92.3%) moderate identify the causative organism. S. pneumoniae patients, and four of six (66.7%) severe patients. urinary antigen test (Binax NOW® S. pneumoniae) Furthermore, in terms of bacteriology, all strains is the method to detect urinary capsule antigen for composed of PSSP (19 strains), PISP (two strains), S. pneumoniae by immunochromatography. It has and PRSP (one strain) were eradicatd.
higher sensitivity than sputum or blood culture,  Although the MIC of penicillin-G was as high as with a sensitivity of 70-80% and a specificity of 80- 4μg10) for PISP and PRSP, administration of 3 g 90%2-5). The JRS guidelines also recommend of SBT/ABPC b. i. d. was efficacious for penicillin- intravenous penicillin for patients with positive S. pneumoniae urinary antigen test requiring  Side effects were drug eruption, increased GOT, increased AMY, and decreased WBC in one patient  Therefore, we evaluated the efficacy of each; however, all were mild, showing high safety. intravenous penicillin (sulbactam/ampicillin: SBT/ The results of Metaanalysis11) also showed high ABPC) in patients with positive S. pneumoniae urinary antigen test requiring hospitalization. SBT/  As shown above, intravenous penicillin ABPC is ABPC compounded with a β-lactamase (sulbactam/ampicillin: SBT/ABPC) for patients inhibitory agent that exhibits a strong antibacterial with positive S. pneumoniae urinary antigen test requiring hospitalization is extremely useful.  Subjects were 26 moderate and 6 severe patients aged 40 to 91 years (72.8±15.5years). Many REFERENCES
patients had underlying respiratory diseases such 1) The committee for JRS guideline in management of as COPD, bronchial asthma, or bronchiectasis, respiratory infections. The JRS Guidelines for the suggesting that pneumonia caused by S. pneumoniae Management of Community-Acquired Pneumonia in adults. Tokyo, Kyorinsya. 2005, pp4-5.
tends to occur in elderly individuals with chronic 2) Murdoch DR, Laing RT, Mills GD, Keralus NC, Town GJ, Mirrett S, Reller LB: Evaluation of  Studies on the effect of SBT/ABPC on adult rapid immunochromatographic test for detection of Streptococcus pneumoniae antigen in urine samples investigation by Williams et al.6) reporting a higher from adults with community-acquired pneumonia. J Clin efficacy than cefamandole in 36 of 37 (97%) patients, and an investigation by Seki et al.7) 3) Smith MD, Derrington P, Evans R, Creek M, Morris R, reporting the same degree of efficacy as PIPC in Dance DA, Cartwright K: Rapid diagnosis of bacteremic Pneumococcal infections in adults by using the Binax 33 of 49 (67.3) patients. Studies on community- NOW Streptococcus pneumoniae urinary antigen test: acquired pneumonia in the elderly include our a prospective, controlled clinical evaluation. J Clin report8) of efficacy in 64 of 83 (77.1%) patients aged 75 years or greater, and an investigation by 4) Dominguez J, Gali N, Blanco S, Pedroso P, Prat Yanagihara et al.9) describing the same efficacy as C, Matas L, Ausina V: Detection of Streptococcus IPM/CS in 32 of 35 (91.4%) patients aged 65 years pneumoniae antigen by a rapid Immunochromatographic assay in urine samples. Chest 119: 243-249, 2001 5) Okimoto N, Hayashi T, Ishiga M, Nanba F, Kishimoto  The present investigation of community-acquired M, Yagi S, Kurihara T, Asaoka N, Tamada S: Positive pneumonia caused by S. pneumoniae alone revealed duration of Streptococcus pneumoniae urinary antigen an excellent clinical effect with efficacy in 28 of test. Medical Postgraduate 47: 294-296, 2009 6) Williams D, Perri M, Zervos MJ: Randomized 9) Yanagihara K, Fukuda Y, Seki M, et al.: Clinical comparative trial with ampicillin/sulbactam versus comparative study of sulbactam/ampicillin and cefamandole in the therapy of community acquired imipenem/cilastatin in elderly patients with community- pneumonia. Eur J Clin Microbiol Infect Dis 13: 293-298, acquired pneumonia. Intern Med 45: 995-999, 2006 10) Niki Y, Hanaki H, Matsumoto T, et al.: Nationwide 7) Seki M, Higashiyama Y, Imamura Y, et al.: A clinical surveillance of bacterial respiratory pathogens comparative study of piperacillin and sulbactam/ conducted by the Japanese Society Of Chemotherapy ampicillin in patients with community-acquired bacterial in 2008: general view of the pathogens’ antibacterial susceptibility. J Infect Chemother 17: 510-523, 2011 8) Okimoto N, Kurihara T, Honda N, Asaoka N, Fujita 11) Zervos MJ, Skupien D, Dmuchowski CF: Metaanalysis K, Ohba H, Nakamura J: Clinical effect of ampicillin of the efficacy and safety of ampicillin/sulbactam in with β-lactamase inhibitor(sulbactam/ampicillin) on the treatment of patients with bacterial infections of the community-acquired pneumonia in the elderly. J Infect lower respiratory tract. Infect Dis Clin Pract 6: 473-481,

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